The current grant application proposes to test the hypothesis that the major biochemical abnormality in psoriasis is a dysfunction of the cyclic AMP regulatory system in the epidermis. It has been shown that elevating the cyclic AMP level in epidermis in vitro lowers the mitotic rate. The converse applies to psoriasis. Recent measurements of cyclic AMP in keratome slices of psoriatic lesions also suggest that the level is low. Thus we propose, at the first stage, to measure the cyclic AMP levels directly in basal layers of normal and psoriatic epidermis with a protein binding method and with a simultaneous adaptation of Lowry's micromethod. Should the first stage experiment reveal a significantly low cyclic AMP in the psoriatic lesion, we will then attempt to investigate a possible cause for the low cyclic AMP; the studies will include comparative kinetics of H3-epinephrine binding to a membrane preparation or to whole cells, of adenyl cyclase and of protein kinase in normal and psoriatic epidermis. Attempts will be made to restore the cyclic AMP level by the addition of possible missing factor(s), e.g. by the addition of phospholipids which may enhance epinephrine sensitivity. In addition, changes in the levels of cyclic AMP in normal and psoriatic epidermis will be followed after successive application of compounds known to affect the cyclic AMP system. The information gained in these studies will be used in designing new or improved therapies for psoriasis.